The invention relates to staurosporine derivatives for treating ocular neovascular disease. More specifically, the invention relates to a method for treating ocular neovascular disease, e.g., retinal neovascularization and choroidal neovascularization, with staurosporine derivatives.
The retina of the eye receives its blood supply from two vascular beds, the retinal vessels which supply the inner two thirds of the retina, and the choroidal vessels which supply the outer one third. Damage to retinal blood vessels resulting in closure of retinal capillaries occurs in several disease processes including diabetic retinopathy, retinopathy of prematurity, branch retinal vein occlusion, and central retinal vein occlusion; they are collectively referred to as ischemic retinopathies. Retinal ischemia results in release of one or more angiogenic factors that stimulate neovascularization. The new vessels break through the internal limiting membrane (ILM) that lines the inner surface of the retina and grow along the outer surface of the vitreous. They recruit many other cells and produce sheets of vessels, cells, and extracellular matrix that exert traction on the retina, often leading to retinal detachment and severe loss of vision.
Choroidal neovascularization occurs in a number of disease processes, the most common of which is age-related macular degeneration. In this condition, the macula, which is especially adapted for acute and detailed vision, is damaged by gradual death of photoreceptor and RPE cells. This constitutes the degeneration part of the disease which results in the gradual loss of central vision. The reason for the cell death is unknown and there is currently no treatment. As the degeneration occurs, there is a tendency for new blood vessels to grow from the choroid to invade the sub-RPE and subretinal spaces. This process is called choroidal neovascularization (CNV) and it often leads to rapid and severe loss of vision from bleeding and scarring. If the CNV is well-delineated and not beneath the center of the fovea, which is true for a small minority of patients, laser treatment can sometimes help. Even when laser is initially successful, there is a high rate of recurrent CNV and loss of vision. A treatment directed at the stimuli for blood vessel growth is needed and would benefit patients with either retinal or choroidal neovascularization.